Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

Hao, Junhua; Лі, Бо; Duan, Huiquan; Zhao, Chenxi; Zhang, Yan; Sun, Chao; Pan, Bin; Liu, Chang; Kong, Xiaohong; Yao, Xuemei; Feng, Shiqing

doi:10.4103/1673-5374.208591

Cited by 53 publications

(41 citation statements)

References 38 publications

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“…Targeting iron is one of the treatment strategies. The iron chelator, DFO, reportedly reduced iron accumulation and lipid peroxidation, while modulating the inflammatory response in SCI ( Paterniti et al, 2010 ; Liu et al, 2011 ; Dinc et al, 2013 ; Hao et al, 2017 ). Experimental evidence indicated that DFO improved motor function recovery when injected intraperitoneally post-SCI ( Paterniti et al, 2010 ; Liu et al, 2011 ; Hao et al, 2017 ).…”

Section: Potential and Emerging Therapy Targeting Ferroptosis In Acutmentioning

confidence: 99%

“…The iron chelator, DFO, reportedly reduced iron accumulation and lipid peroxidation, while modulating the inflammatory response in SCI ( Paterniti et al, 2010 ; Liu et al, 2011 ; Dinc et al, 2013 ; Hao et al, 2017 ). Experimental evidence indicated that DFO improved motor function recovery when injected intraperitoneally post-SCI ( Paterniti et al, 2010 ; Liu et al, 2011 ; Hao et al, 2017 ). Moreover, DFO showed neuroprotective effects comparable with methylprednisolone, an effective antioxidant agent that is contentious for the treatment of SCI because of harmful side effects ( Dinc et al, 2013 ; Silva et al, 2014 ).…”

Section: Potential and Emerging Therapy Targeting Ferroptosis In Acutmentioning

confidence: 99%

“…Notably, following the rupture of the blood-spinal cord barrier and blood vessels, hemorrhage occurs in the acute phase of SCI and may last for days ( Tran et al, 2018 ). Like other acute CNS diseases, ferroptosis occurs in SCI, and is accompanied by increased iron and accumulated ROS at the site of injury ( Liu et al, 2011 ; Visavadiya et al, 2016 ; Hao et al, 2017 ), as well as excessive lipid peroxidation ( Dinc et al, 2013 ; Hu et al, 2017 ). This phenomenon is more apparent during the first several hours ( Liu et al, 2004 ).…”

Section: The Role and Mechanism Of Ferroptosis In Acute Cns Injuriesmentioning

confidence: 99%

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Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?

Shen

Lin

et al. 2020

Front. Cell Dev. Biol.

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Acute central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI) present a grave health care challenge worldwide due to high morbidity and mortality, as well as limited clinical therapeutic strategies. Established literature has shown that oxidative stress (OS), inflammation, excitotoxicity, and apoptosis play important roles in the pathophysiological processes of acute CNS injuries. Recently, there have been many studies on the topic of ferroptosis, a form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxidation. Some studies have revealed an emerging connection between acute CNS injuries and ferroptosis. Ferroptosis, induced by the abnormal metabolism of lipids, glutathione (GSH), and iron, can accelerate acute CNS injuries. However, pharmaceutical agents, such as iron chelators, ferrostatin-1 (Fer-1), and liproxstatin-1 (Lip-1), can inhibit ferroptosis and may have neuroprotective effects after acute CNS injuries. However, the specific mechanisms underlying this connection has not yet been clearly elucidated. In this paper, we discuss the general mechanisms of ferroptosis and its role in stroke, TBI, and SCI. We also summarize ferroptosis-related drugs and highlight the potential therapeutic strategies in treating various acute CNS injuries. Additionally, this paper suggests a testable hypothesis that ferroptosis may be a novel direction for further research of acute CNS injuries by providing corresponding evidence.

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Section: Potential and Emerging Therapy Targeting Ferroptosis In Acutmentioning

confidence: 99%

Section: Potential and Emerging Therapy Targeting Ferroptosis In Acutmentioning

confidence: 99%

Section: The Role and Mechanism Of Ferroptosis In Acute Cns Injuriesmentioning

confidence: 99%

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Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?

Shen

Lin

et al. 2020

Front. Cell Dev. Biol.

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“…Our team utilized deferoxamine (DFO), an iron chelator, in the repair of SCI. We found that the application of DFO could decrease the total iron ion level, TNFα, IL1-β and caspase-3 expression and glial scar formation after SCI and promote the survival of cells and recovery of motor function 24 .…”

Section: Molecular Imbalancementioning

confidence: 81%

“…1 ①) A direct rupture of the local capillaries induces bleeding into the parenchyma of the spinal cord, especially into the gray matter 23 , which could cause increased release of cytokines and chemokines from macrophages, microglia and astrocytes into the extracellular space. And the presence of red blood cells/heme in parenchyma, a rich source of iron, is likely to induce free radicals and be toxic 24 , which is a potential mechanism for ferroptosis. Venous stasis and distension would further cause the accumulation of proteinaceous fluid in the tissues, leading to edema 25 .…”

Section: Tissue Imbalancementioning

confidence: 99%

Microenvironment Imbalance of Spinal Cord Injury

et al. 2018

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Spinal cord injury (SCI), for which there currently is no cure, is a heavy burden on patient physiology and psychology. The microenvironment of the injured spinal cord is complicated. According to our previous work and the advancements in SCI research, ‘microenvironment imbalance’ is the main cause of the poor regeneration and recovery of SCI. Microenvironment imbalance is defined as an increase in inhibitory factors and decrease in promoting factors for tissues, cells and molecules at different times and spaces. There are imbalance of hemorrhage and ischemia, glial scar formation, demyelination and re-myelination at the tissue’s level. The cellular level imbalance involves an imbalance in the differentiation of endogenous stem cells and the transformation phenotypes of microglia and macrophages. The molecular level includes an imbalance of neurotrophic factors and their pro-peptides, cytokines, and chemokines. The imbalanced microenvironment of the spinal cord impairs regeneration and functional recovery. This review will aid in the understanding of the pathological processes involved in and the development of comprehensive treatments for SCI.

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miR‐22‐3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis

Wang

et al. 2019

Journal Cellular Physiology

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Spinal cord injury (SCI) is a devastating disease. Strategies that enhance the intrinsic regenerative ability are very important for the recovery of SCI to radically prevent the occurrence of sensory disorders. Epidermal growth factor (EGF) showed a limited effect on the growth of primary sensory neuron neurites due to the degradation of phosphorylated-epidermal growth factor receptor (p-EGFR) in a manner dependent on Casitas B-lineage lymphoma (CBL) (an E3 ubiquitin-protein ligase). MiR-22-3p predicted from four databases could target CBL to inhibit the expression of CBL, increase p-EGFR levels and neurites length via STAT3/GAP43 pathway rather than Erk1/2 axis. EGF, EGFR, and miR-22-3p were downregulated sharply after injury. In vivo miR-22-3p Agomir application could regulate CBL/p-EGFR/p-STAT3/GAP43/p-GAP43 axis, and restore spinal cord sensory conductive function. This study clarified the mechanism of the limited promotion effect of EGF on adult primary sensory neuron neurite and targeting miR-22-3p could be a novel strategy to treat sensory dysfunction after SCI. K E Y W O R D Scasitas b-lineage lymphoma, epidermal growth factor, epidermal growth factor receptor, miR-22-3p, primary sensory neuron, spinal cord injury

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Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

Cited by 53 publications

References 38 publications

Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?

Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?

Microenvironment Imbalance of Spinal Cord Injury

miR‐22‐3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis

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